Brain microvasculature has a common topology with local differences in geometry that match metabolic load

• Published in: Neuron (Cambridge, Mass.) Vol. 109; no. 7; pp. 1168 - 1187.e13
• Main Authors: Ji, Xiang, Ferreira, Tiago, Friedman, Beth, Liu, Rui, Liechty, Hannah, Bas, Erhan, Chandrashekar, Jayaram, Kleinfeld, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.04.2021; Elsevier Limited
• Subjects: Algorithms; Alzheimer's disease; Animals; Anisotropy; Brain; Brain - diagnostic imaging; Brain Chemistry - physiology; Brain mapping; Capillaries; Capillaries - physiology; Cerebrovascular Circulation - physiology; connectome; Fluorescent Dyes; fMRI; Functional magnetic resonance imaging; Geometry; glucose; graph; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Microvasculature; Microvessels - anatomy & histology; Microvessels - diagnostic imaging; Microvessels - metabolism; Neural networks; oxygen; Oxygen Consumption - physiology; Oxygen tension; percolation; perfusion; stroke; fMRI; glucose; percolation; perfusion; anisotropy; connectome; oxygen; stroke; graph
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2021.02.006

The microvasculature underlies the supply networks that support neuronal activity within heterogeneous brain regions. What are common versus heterogeneous aspects of the connectivity, density, and orientation of capillary networks? To address this, we imaged, reconstructed, and analyzed the microvasculature connectome in whole adult mice brains with sub-micrometer resolution. Graph analysis revealed common network topology across the brain that leads to a shared structural robustness against the rarefaction of vessels. Geometrical analysis, based on anatomically accurate reconstructions, uncovered a scaling law that links length density, i.e., the length of vessel per volume, with tissue-to-vessel distances. We then derive a formula that connects regional differences in metabolism to differences in length density and, further, predicts a common value of maximum tissue oxygen tension across the brain. Last, the orientation of capillaries is weakly anisotropic with the exception of a few strongly anisotropic regions; this variation can impact the interpretation of fMRI data. [Display omitted] •Whole mouse brain microvascular connectome at sub-micrometer resolution•Common network topology leads to a shared structural robustness against damage•Regional network geometry linked to metabolism via diffusive transport of oxygen•Large fraction of brain microvasculature is significantly anisotropic Ji et al. constructed the whole mouse brain microvascular connectome. Their analysis reveals a common network topology that leads to shared robustness against vessel rarefaction and stalled RBCs, while a heterogeneous network geometry matches the rate of regional resting metabolism to maintain a common maximum oxygen tension throughout the brain.